Basic Research in Cardiology最新文献

{"title":"Amyloid beta 42 disrupts cardiac function in Alzheimer's disease mice via SLC31A1 upregulation-mediated cuproptosis.","authors":"Wenjun Xiong, Zikang Luo, Hong Wang, Qiaozhu Su, Haitao Wang, Jiangping Xu, Wenhua Zheng","doi":"10.1007/s00395-026-01163-y","DOIUrl":"10.1007/s00395-026-01163-y","url":null,"abstract":"<p><p>Background Alzheimer's disease (AD) is a complex systemic disorder that extends beyond the central nervous system, exerting pathological effects on the heart. Epidemiological studies have consistently shown that individuals with AD often exhibit impaired cardiac function. While amyloid-beta (Aβ) is a key pathological hallmark of AD, primarily known for forming oligomers and fibrils in the brain, emerging evidence suggests that Aβ also exerts detrimental effects on the myocardium. Despite these observations, the precise mechanisms through which AD contributes to the onset or progression of heart failure (HF) remain poorly understood. This study aims to elucidate the underlying links between AD and HF, with a specific focus on the pathogenic role of Aβ in promoting cardiac dysfunction within experimental models of AD. Methods Cardiomyocytes and 3 × Tg-AD mouse models were used to investigate Aβ-induced cardiotoxicity and to determine the mode of myocardial cell death. We assessed cell viability, intracellular copper levels, and markers of cuproptosis. Mitochondrial oxidative respiration, ATP production, and reactive oxygen species (ROS) levels were also evaluated. Myocardial pathology and cuproptosis-related proteins were detected by histochemistry and immunoblotting. Results In 3 × Tg-AD mice, elevated cardiac Aβ paralleled cardiac dysfunction, promoted cuproptosis in cardiomyocytes, and this effect was counteracted by the copper chelator TTM which inhibited myocardial copper uptake and protected cardiac function. Building on this in vivo observation, we further investigated the mechanism in vitro and found that Aβ upregulated the copper importer SLC31A1 in vitro. Furthermore, Aβ1-42 acted synergistically with CuCl₂ or elesclomol-CuCl₂ to exacerbate cardiomyocyte death. This synergy increased intracellular copper accumulation, triggered Fe-S cluster protein loss, and promoted DLAT oligomerization-hallmarks of cuproptosis. These cuproptosis-associated changes suppressed mitochondrial oxidative respiration, decreased ATP synthesis, and elevated ROS levels. Importantly, interference with SLC31A1 expression in vivo and in vitro partially inhibited cuproptosis and protected mitochondrial or cardiac function. Conclusion Aβ1-42 disrupts copper homeostasis by upregulating SLC31A1, thereby exacerbating myocardial cuproptosis and impairing cardiac function in AD. This novel mechanism highlights SLC31A1-mediated cuproptosis as a potential therapeutic target for preserving cardiac health in AD.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"285-299"},"PeriodicalIF":9.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote ischemic conditioning for safe cardioprotection in cardio-oncology?","authors":"Matthias Totzeck, Tienush Rassaf","doi":"10.1007/s00395-026-01161-0","DOIUrl":"10.1007/s00395-026-01161-0","url":null,"abstract":"","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"227-230"},"PeriodicalIF":9.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological reactivation of autophagic flux by natural compounds or synthetic cell-permeable peptide prevents doxorubicin-induced cardiomyopathy.","authors":"Leonardo Schirone,Daniele Vecchio,Valentina Valenti,Vittorio Picchio,Sonia Schiavon,Luca D'Ambrosio,Flavio di Nonno,Selenia Miglietta,Michela Relucenti,Luca Madaro,Silvia Palmerio,Claudia Cozzolino,Margherita Litterio,Gianmarco Sarto,Beatrice Simeone,Nicola Moro,Shazia Tahir,Tania Zaglia,Giuseppe Biondi Zoccai,Elena De Falco,Vincenzo Petrozza,Ernesto Greco,Giacomo Frati,Maurizio Forte,Sebastiano Sciarretta","doi":"10.1007/s00395-026-01174-9","DOIUrl":"https://doi.org/10.1007/s00395-026-01174-9","url":null,"abstract":"Therapeutic strategies to limit doxorubicin (DOX)-induced cardiomyopathy are still limited due to incomplete characterization of the underlying molecular mechanisms. The exogenous activation of autophagy was reported to exert cardioprotective effects in preclinical models of cardiovascular diseases. We tested whether restoration of autophagy by different pharmacological approaches can reduce DOX-induced cardiomyopathy. A validated preclinical murine model of DOX-induced cardiotoxicity (final cumulative dose of 15 mg/kg) was used to test the cardiac effects of both natural (trehalose and spermidine) and synthetic (Tat-Beclin 1 D11) activators of autophagy. Cardiac function was evaluated by echocardiographic analyses. We performed histological analyses (Masson trichrome staining, TUNEL assay) to investigate fibrosis and apoptosis. Biomolecular analyses, confocal and transmission electron microscopy were used to assess levels of autophagy, autophagic flux, mitophagy and mitochondrial alterations. We also evaluated the effects of autophagy activators in a validated syngeneic model with subcutaneous injection of breast cancer cells treated with DOX. We found that DOX-induced cardiotoxicity is associated with impaired autophagic flux (accumulation of LC3-II and p62). Reactivation of autophagic flux by trehalose or spermidine rescues cardiac function and cardiomyocyte survival in mice treated with DOX, along with an overall amelioration of mitochondrial health and mitophagy. Selective reactivation of autophagy by Tat-Beclin 1 D11 also recapitulates the protective effects exerted by trehalose and spermidine. Autophagy activators preserve cardiac function without affecting the antineoplastic effects of DOX in mice with cancer. Boosting autophagic flux is a suitable therapeutic approach to prevent cardiotoxicity induced by anthracyclines.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"21 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147536289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high-fat diet nutritional intervention reprograms cardiac metabolism and improves systolic function in a pig model of heart failure with reduced ejection fraction.","authors":"Carlos Galán-Arriola,Daniel Pérez-Camargo,Alessia Ferrarini,Annalaura Mastrangelo,María Isabel Higuero-Verdejo,Gonzalo Javier López-Martín,Ana Devesa,Rocío Villena Gutiérrez,Miguel Fernández-Tocino,Anabel Díaz-Guerra,Lourdes Montero-Cruces,Manuel Carnero,Rodrigo Fernández-Jiménez,Valentin Fuster,Javier Sánchez-González,Borja Ibáñez","doi":"10.1007/s00395-026-01171-y","DOIUrl":"https://doi.org/10.1007/s00395-026-01171-y","url":null,"abstract":"Most forms of heart failure are characterized by a metabolic switch from the use of fatty acids to glucose as the main fuel source for ATP generation in the myocardium. Whether metabolic reprogramming is a therapeutic target remains controversial. In this study, heart failure with reduced ejection fraction (HFrEF) and metabolic switch (i.e., increased myocardial glucose uptake) was induced in pigs by generating viable dysfunctional myocardium secondary to progressive coronary artery stenosis. Pigs (n = 19) were then randomized to a high-fat diet (HFD, chow diet supplemented with 20% lard) or control diet (no supplementation) for two months. Pre- and post-nutritional treatment contrast-enhanced cardiac magnetic resonance (CMR) and 18FDG-PET/CT studies were performed. Hearts were then harvested for further analysis. LVEF significantly improved in pigs receiving the 2-month HFD (38% [33, 43] to 54% [47, 62], p = 0.036) but remained unchanged in control-diet pigs (36% [35, 45] to 41% [38, 43], p = 0.24). HFD-fed pigs had a smaller extent of fibrosis after the dietary intervention (late gadolinium enhancement 0.45% LV [0.17, 1.67] vs 6.23 [5.54, 9.57], p = 0.0047). On 18FDG-PET, a reversion of the metabolic reprogramming in the LAD-dysfunctional myocardium was observed only in HFD-fed pigs (0.46 counts [0.21, 0.65] vs 1.80 [1.53, 2.83], p = 0.016). Transmission electron microscopy of explanted hearts revealed less fragmented mitochondrial and a lower lipid droplet density in cardiomyocytes from HFD-fed pigs (38 per 10 µm3 [34, 50] vs 96 [78, 124], p = 0.022), and this was accompanied by increased expression of genes involved in fatty acid metabolism and downregulation of genes encoding glucose import proteins. In conclusion, in a large animal model of HFrEF secondary to myocardial dysfunction with a metabolic switch, a nutritional intervention based on HFD feeding was associated with a cardiac metabolic restoration of fatty acid substrate use, restoration of cardiomyocyte lipid trafficking and significantly improved systolic function.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"61 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147524490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term blockade of E-prostanoid 3 receptor mitigates necroinflammation and ameliorates ischemia/reperfusion- and doxorubicin-induced acute myocardial injury.","authors":"Dong He,Yequn Chen,Jiahui Ge,Jinwei Guo,Zhen Wang,Gang Yu,Shiwan Wu,Jing Leng,Bin Wang,Shunyu Pang,Xijian Chen,Yineng Xu,Cheng Peng,Jianye Yang,Shijun Liu,Anhong Cai,Zhengpeng Zeng,Xinya Shi,Siyi Ling,Yukuan Chen,Yingbi Zhou,Bin Liu","doi":"10.1007/s00395-026-01173-w","DOIUrl":"https://doi.org/10.1007/s00395-026-01173-w","url":null,"abstract":"E-prostanoid 3 receptor (EP3) plays an important role in maintaining normal heart growth and development, and its activation may drive acute inflammation and influence intracellular Ca2+ level. The effects of targeting EP3 on myocardial injury have been very controversial. We aimed to elucidate roles of EP3 in both innate immune cells and cardiomyocytes during the acute phase of acute myocardial injury. Wild-type, global Ep3 knockout (Ep3-/-), myeloid conditional Ep3-deficient (Ep3F/F;Lyz2Cre) and tamoxifen-induced cardiomyocyte-specific Ep3 knockout (Ep3F/F;Myh6MerCreMer) mice were subjected to regional ischemia/reperfusion (I/R) or acute doxorubicin (DOX) treatment. Inflammation, prostaglandin production, and damage-associated molecular pattern (DAMP) release were induced in acute myocardial injury in mice and patients. Injury caused by I/R or DOX was substantially ameliorated in EP3 antagonist-treated wild-types, but not in their Ep3-/- counterparts. I/R injury was alleviated in Ep3F/F;Lyz2Cre rodents and Ep3F/F;Myh6MerCreMer mice at 1 week after the administration of tamoxifen, but exacerbated in the latter at 8 weeks. Germline Ep3-/- hearts were predisposed to abnormalities. Antagonism or myeloid deficiency of EP3 ameliorated I/R injury by suppressing inflammation and regulating necrosis pathways, constituting an auto-amplification loop of necroinflammation. EP3 disruption in cardiomyocytes prevented the agonist-induced increase of diastolic Ca2+ level. Short-term EP3 abrogation in cardiomyocytes also reduced local and systemic inflammation after I/R. Collectively, long-term EP3 abrogation predisposes hearts to abnormalities and is detrimental; however, its deficiency in myeloid cells or transient deletion in cardiomyocytes convergently mitigates necroinflammation and alleviates acute myocardial injury, indicating short-term EP3 blockade is a potentially promising therapeutic strategy for such diseases.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"33 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights in ischemia/reperfusion injury and cardioprotection: neglected and emerging pathways and therapeutic targets for a personalized therapy.","authors":"Pasquale Pagliaro,C Penna,S Femminò,F G P Welt","doi":"10.1007/s00395-026-01167-8","DOIUrl":"https://doi.org/10.1007/s00395-026-01167-8","url":null,"abstract":"Despite extensive preclinical research identifying molecular targets and cardioprotective strategies, translation into effective clinical therapies remains challenging. Cardioprotection aims to mitigate ischemia/reperfusion injury (IRI) by modulating molecular pathways, such as the Reperfusion Injury Salvage Kinase (RISK) and Survivor Activating Factor Enhancement (SAFE) pathways, as well as autophagy, inflammation, and regulated cell death, to preserve myocardial function. However, a major limitation lies in the robustness of preclinical evidence. Many experimental studies rely on simplified models that fail to reproduce the complexity of human cardiac pathophysiology, resulting in inconsistent and poorly reproducible cardioprotective effects. It is likely that RISK-SAFE pathways represent an oversimplified framework. Moreover, most experimental approaches are cardiomyocyte-centered, overlooking the critical role of the vessels in IRI. Clinical translation is further compromised by patient-related factors, including comorbidities (e.g., diabetes, hypertension), concomitant medications, and heterogeneity in reperfusion protocols, all of which attenuate cardioprotective efficacy. Additional variables, such as timing of intervention and species differences, further contribute to translational failure. Emerging approaches include pharmacological therapies (e.g., SGLT2 inhibitors, PARP inhibitors, necroptosis and ferroptosis blockers, NLRP3-targeting compounds), cell- and organelle-based strategies (e.g., mitochondrial transplantation, extracellular vesicles, non-coding RNAs), and mechanical/device-based interventions (e.g., left ventricular unloading, ischemic conditioning, controlled reperfusion, selective intracoronary hypothermia). Future research should emphasize multi-target interventions, optimized timing and delivery, and advanced tools, such as nanocarriers, gene therapy, computational modeling, and adaptive clinical trials. Strengthening the robustness of preclinical models, including human ex vivo cardiac systems, remains essential to bridge the translational gap and improve the clinical success of cardioprotective therapies.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"8 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARKIN overexpression confers cardioprotection via suppressing the mtDNA-cGAS-STING axis in myocardial ischemia/reperfusion injury.","authors":"Yujing Li,Yuhan Wang,Hao Zhang,Pengfei Xu,Xiaosu Yuan,Hailong Yuan,Chaofan Yang,Yanan Zhou,Jianghua Shen,Heng Du,Zeyu Gao,Jingyi Zang,Siwen Liang,Jing Qu,Moshi Song","doi":"10.1007/s00395-026-01169-6","DOIUrl":"https://doi.org/10.1007/s00395-026-01169-6","url":null,"abstract":"Myocardial ischemia/reperfusion (I/R) injury is exacerbated by inflammation, yet the upstream triggers of this cascade and their amenability to therapeutic intervention remain unclear. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a driver of sterile inflammation in I/R injury, but whether its activation can be suppressed via enhanced mitochondrial quality control has not been explored. We hypothesized that augmenting PARKIN-mediated mitophagy would limit cGAS-STING activation and attenuate I/R injury by clearing damaged mitochondria and preventing the release of its agonist, mitochondrial DNA (mtDNA). Cardiomyocyte-specific PARKIN overexpression in mice was well tolerated at baseline and conferred cardioprotection following I/R injury, attenuating adverse remodeling and preserving cardiac function. Mechanistically, PARKIN overexpression enhanced mitophagy, which limited cytosolic mtDNA accumulation, thereby inhibiting cGAS-STING activation and its downstream inflammatory response. The therapeutic potential of this pathway was further supported by lentiviral PARKIN delivery in wild-type mouse hearts, which also improved cardiac outcomes following I/R injury. Taken together, our findings delineate a PARKIN-mtDNA-cGAS-STING axis as a regulatory mechanism of I/R injury and support PARKIN augmentation as a potential therapeutic strategy.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"17 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time course of early and delayed myocardial protection induced by vagal nerve stimulation preconditioning.","authors":"Verena B Franco-Riveros,Jazmín Kelly,Timoteo Marchini,Virginia Pérez,Eduardo A Bernatené,Elizabeth Robello,Mónica Galleano,Martín Donato,Pablo Evelson,Ricardo J Gelpi,Bruno Buchholz","doi":"10.1007/s00395-026-01165-w","DOIUrl":"https://doi.org/10.1007/s00395-026-01165-w","url":null,"abstract":"We previously reported that pre-ischemic vagus nerve stimulation (VNS) protects against myocardial ischemia, resembling classical ischemic preconditioning (cPC). This study investigates the time course and mechanisms underlying VNS-induced cardioprotection. Male FVB/N mice (3-5 months) underwent 30 min regional myocardial ischemia followed by 120 min reperfusion (IR). Ten-minute right-sided cervical VNS was delivered at defined intervals before ischemia to assess early and delayed protective windows. Risk area (RA) and infarct size (IS) were quantified using Evans Blue/tetrazolium staining. Myocardial phosphorylation of protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), inducible nitric oxide synthase (iNOS), and mitochondrial respiration were evaluated. IR controls exhibited an IS of 57 ± 7% of the RA. VNS elicited a biphasic cardioprotective response. Early protection was observed when ischemia occurred 5 min, 3 h, or 6 h after VNS, with IS reduced to 44 ± 8%, 34 ± 7%, and 36 ± 9%, respectively (p ≤ 0.0001 vs. IR). This phase depended on muscarinic acetylcholine receptor (mAChR) activation, involved Akt/GSK-3β/NOS signaling, and was associated with preserved mitochondrial respiration. The protective effect was abolished by atropine, NG-nitro-L-arginine methyl ester (L-NAME), or the mitoKATP channel blocker 5-hydroxydecanoate (5HD). Delayed protection emerged 72 h after VNS, reducing IS to 42 ± 7% (p = 0.0001 vs. IR). This phase was independent of mitochondrial respiration preservation and required mAChR and iNOS signaling, as it was abolished by atropine, L-NAME, or the selective iNOS inhibitor 1400W, but not by 5HD. These findings identify pre-ischemic VNS as a biphasic cardioprotective strategy with distinct phase-specific mechanisms, highlighting its potential therapeutic relevance in limiting IR injury.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"263 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain natriuretic peptide protects against acute pulmonary embolism-induced pulmonary vasoconstriction through natriuretic peptide receptor C.","authors":"Yizhuo Gao,Shiqi Liu,Zhichun Gu,Xuejiao Wei,Xue Han,Shibo Wei,Jing Yang,Yuchen Liu,Dong Jia","doi":"10.1007/s00395-026-01166-9","DOIUrl":"https://doi.org/10.1007/s00395-026-01166-9","url":null,"abstract":"Acute pulmonary embolism (PE) remains a leading cause of cardiovascular mortality, driven primarily by a sudden increase in pulmonary artery (PA) resistance. Brain Natriuretic Peptide (BNP) may hold promise for reducing PA resistance. However, its role and mechanism in acute PE are not yet fully understood. This study aims to determine whether BNP alleviates PE-induced pulmonary vasoconstriction by targeting Natriuretic Peptide Receptor C (NPRC) and evaluate its therapeutic potential. Here, we established an acute PE rat model using autologous thrombi, and right ventricle (RV) pressure was monitored to approximate PA resistance. A small group of intermediate-high-risk acute PE patients were observed, who received BNP in addition to anticoagulation, and their clinical outcomes were compared to matched patients receiving anticoagulation alone. BNP at varying doses was administered to optimize therapeutic efficacy in the acute PE rat model. Mechanistic studies assessed BNP's impact on oxidative stress in PA endothelium. In the rats, BNP infusion significantly reduced RV pressure overload and improved survival. Clinically, patients receiving adjunctive BNP experienced more rapid improvement in heart rate, oxygen saturation, and blood pressure stability than anticoagulation alone. BNP decreased NADPH oxidase 2-dependent ROS levels in rats' PA endothelium, thereby reducing myosin light chain phosphorylation in smooth muscle. NPRC, as the central receptor, antagonizes the protective effect of BNP. Collectively, BNP offers a novel choice to mitigate PE-induced pulmonary vasoconstriction via NPRC-mediated mechanisms, which support BNP's therapeutic potential for intermediate-high-risk PE.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"403 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artery tertiary lymphoid organs, neuro-immune interaction and their mediators in atherosclerosis.","authors":"Silvia Ortona,Caterina Ivaldo,Luca Liberale,Federico Carbone,Fabrizio Montecucco,Martina Bastianon,Maddalena Mastrogiacomo,Domenico Palombo,Giovanni Pratesi,Chiara Barisione","doi":"10.1007/s00395-026-01164-x","DOIUrl":"https://doi.org/10.1007/s00395-026-01164-x","url":null,"abstract":"Atherosclerosis is a chronic inflammatory disease characterized by the irreversible remodeling of the arterial wall; severe atherosclerotic lesions may lead to life-threatening consequences such as major ischemic events (i.e., myocardial infarction (MI) and stroke) and abdominal aortic aneurysm (AAA) rupture. The severity of the lesions is determined by multiple risk factors that cause systemic and cellular metabolic changes, oxidative damage, cell senescence, and immune activation involving both leukocytes and vascular cells. In advanced stages, macrophage infiltration, alterations of the load-bearing collagenous matrix, and the presence of microcalcifications are the main drivers of plaque vulnerability. Over the last decade, the presence of artery tertiary lymphoid organs (ATLOs) has been established. These structures form during progressive atherosclerosis in the adventitia of large arteries and represent highly organized niches composed of T and B lymphocytes and innate immune cells. More recently, the presence of nerve fibers and the contribution of both the central (CNS) and peripheral (PeriphNS) nervous systems, through the action of sympathetic, parasympathetic, and somatosensory pathways regulating ATLO composition have been demonstrated. However, their role in atherosclerosis progression remains debated. This review explores the architecture of ATLOs and their neuroimmune interactions with the spleen, as a central neuroimmune organ, in atherosclerosis progression, with a particular focus on carotid stenosis and AAA. Furthermore, it highlights the neuronal mediators that could act as biomarkers of plaque instability and promising pharmacological targets. Finally, while still in the preclinical phase, it explores future prospects for integrating neuroimmune-based therapies into current clinical management of atherosclerosis.","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"21 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}